NK cells promote peritoneal xenograft rejection through an IFN-gamma-dependent mechanism
- Author(s)
- Lin, ML; Zhan, YF; Nutt, SL; Brady, J; Wojtasiak, M; Brooks, AG; Lew, AM;
- Details
- Publication Year 2006-11,Volume 13,Issue #6,Page 536-546
- Journal Title
- XENOTRANSPLANTATION
- Publication Type
- Journal Article
- Abstract
- Background: Natural killer (NK) cells have emerged as major players in anti-viral and anti-tumour immune responses. Like cytotoxic T lymphocytes (CTL), they express perforin and are potent secretors of gamma-interferon (IFN-gamma). However, there is conflicting evidence about their role in mediating rejection of xenogeneic tissue. Methods: A pig-to-mouse peritoneal cell model of xenotransplantation was used to investigate the effect of NK deficiency on xenograft recovery and the possible mechanisms behind this NK-mediated graft rejection. gamma c(-/-)RAG(-/-) mice were used as a model of NK deficiency. Additionally, NK cells were depleted in RAG(-/-) mice using anti-asialo GM1. The contributions of IFN-gamma, perforin and NKT cells were studied using knock-out mice that were depleted in vivo of T cells. Mice were injected with 10(7) pig cells intraperitoneally and peritoneal fluid was assessed 5 days later for xenograft recovery and phenotypic analysis. The requirement for NK cells for xenograft rejection was also assessed using luciferase-transfected porcine cells in a renal subcapsular model of transplantation. Results: Pig cell recovery was enhanced in both gamma c(-/-)RAG(-/-) and NK-depleted RAG(-/-) mice when compared with RAG(-/-) control mice. IFN-gamma(-/-) mice depleted of T cells also demonstrated superior graft survival compared with their B6 counterparts. However, there were minimal graft survival differences between Pfp(-/-) and B6 control mice. Similarly, a deficiency in NKT cells did not improve pig xenograft recovery from the peritoneum of these mice. Conclusions: Therefore, we conclude that NK cells, but not NKT cells, are important mediators of xenograft rejection in the peritoneal cavity, and that their role may be unmasked in the absence of T cells. The mechanism for this xenorejection appears to involve IFN-gamma but is perforin independent.
- Publisher
- BLACKWELL PUBLISHING
- Keywords
- NATURAL-KILLER-CELLS; CYTOTOXIC T-LYMPHOCYTES; INTERFERON-GAMMA; IMMUNE-RESPONSES; DEFICIENT MICE; DEPLETED MICE; PORCINE CELLS; MACROPHAGES; INNATE; TRANSPLANTATION
- Publisher's Version
- https://doi.org/10.1111/j.1399-3089.2006.00348.x
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- Refer to copyright notice on published article.
Creation Date: 2006-11-01 12:00:00